【摘要】：炎癥性腸病(Inflammatory bowel disease,IBD)是一類以慢性炎癥為特征的腸道炎癥疾病。引發(fā)該病癥的因素繁多,有效的宿主防御機(jī)制對(duì)于抵御IBD十分重要。S100A4是S100家族中的一員,在炎癥中的作用尚不清楚。因此,本試驗(yàn)分別給S100A4基因敲除小鼠(S100A4-/-)和野生型小鼠(Wild type,WT)灌胃2×109 CFU(Colony-forming unit,CFU)的檸檬酸桿菌(Citrobacter rodentium,C.rodentium),建立腸炎模型。采用組織學(xué)、細(xì)胞學(xué)和分子生物學(xué)等技術(shù)方法探究S100A4在炎癥中的作用及分子機(jī)制。結(jié)果表明S100A4在C.rodentium誘導(dǎo)的小鼠腸炎模型中的表達(dá)顯著上調(diào)(P0.01)。S100A4-/-小鼠相對(duì)于WT小鼠體重下降不明顯(P0.01),結(jié)腸病理?yè)p傷程度減輕(P0.05),結(jié)腸中趨化因子和促炎因子的表達(dá)顯著下調(diào)(P0.05),結(jié)腸炎癥細(xì)胞的浸潤(rùn)減少(P0.01),結(jié)腸炎癥相關(guān)蛋白p65的磷酸化水平顯著下調(diào)。說(shuō)明S100A4能夠促進(jìn)結(jié)腸炎的發(fā)展。S100A4-/-小鼠結(jié)腸Ki-67的陽(yáng)性細(xì)胞率顯著下降(P0.05);WT小鼠結(jié)腸中增殖相關(guān)蛋白Stat3、Erk的磷酸化水平顯著上調(diào)。說(shuō)明S100A4促進(jìn)C.rodentium誘導(dǎo)的小鼠結(jié)腸上皮細(xì)胞的增殖。進(jìn)一步研究發(fā)現(xiàn)S100A4能夠增加C.rodentium對(duì)小鼠結(jié)腸和CT26細(xì)胞的黏附(P0.05);整合素β1(Integrinβ1)在WT小鼠結(jié)腸中和S100A4蛋白處理的CT26細(xì)胞中的表達(dá)顯著上調(diào)(P0.05)。上述結(jié)果說(shuō)明S100A4能夠通過(guò)上調(diào)Integrinβ1的表達(dá)增加C.rodentium對(duì)腸道上皮細(xì)胞的黏附,從而促進(jìn)結(jié)腸炎的發(fā)展。本實(shí)驗(yàn)為探究S100A4在結(jié)腸炎中的作用及機(jī)制提供了可信的理論依據(jù),可為相關(guān)科學(xué)研究及醫(yī)學(xué)臨床治療提供參考。
[Abstract]:Inflammatory bowel disease (Inflammatory bowel disease,IBD) is a kind of intestinal inflammatory disease characterized by chronic inflammation. There are many factors contributing to the disease, and effective host defense mechanisms are important to resist IBD. S100A4 is a member of the S100 family and its role in inflammation is unclear. Therefore, the S100A4 knockout mice (S100A4-r-) and the wild-type mice (Wild type,WT) were given intragastric administration of 2 脳 10 ~ 9 CFU (Colony-forming unit,CFU) citrate bacilli (Citrobacter rodentium,C.rodentium) to establish enteritis models. The role and molecular mechanism of S100A4 in inflammation were investigated by means of histology, cytology and molecular biology. The results showed that the expression of S100A4 was significantly up-regulated in C.rodentium induced mouse enteritis (P0.01), the weight loss of S100A4-r-m- mice was not significant compared with that of WT mice (P0.01), and the degree of colonic pathological injury was decreased (P0.05). The expression of chemokines and pro-inflammatory factors in colon was significantly down-regulated (P0.05), the infiltration of colitis cells was decreased (P0.01), and the phosphorylation level of p65 was significantly down-regulated. The results showed that S100A4 could promote the development of colitis. The positive rate of Ki-67 in S100A4-r-mouse colon decreased significantly (P0.05) the phosphorylation level of proliferation-associated protein Stat3,Erk in colon of); WT mice was up-regulated. The results showed that S100A4 promoted the proliferation of mouse colon epithelial cells induced by C.rodentium. Further studies showed that S100A4 could increase the adhesion of C.rodentium to mouse colon and CT26 cells (P0.05), and the expression of integrin 尾 1 (Integrin 尾 1) in WT mice colon and CT26 cells treated with S100A4 protein was significantly up-regulated (P0.05). These results suggest that S100A4 can promote the development of colitis by upregulating the expression of Integrin 尾 1 and increasing the adhesion of C.rodentium to intestinal epithelial cells. This study provides a reliable theoretical basis for exploring the role and mechanism of S100A4 in colitis, and provides a reference for related scientific research and medical clinical treatment.
【學(xué)位授予單位】：東北師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R574.62

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1 胡仁偉;歐陽(yáng)欽;陳曦;常玉英;白愛(ài)平;王瑞華;張虎;;近15年我國(guó)炎癥性腸病文獻(xiàn)分析[J];胃腸病學(xué);2007年02期

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本文編號(hào)：2389712